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Paclitaxel use in pregnancy: neonatal follow-up of infants with positive detection of intact paclitaxel and metabolites in meconium at birth

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Abstract

Paclitaxel is often excluded during pregnancy for women with breast cancer due to limited neonatal follow-up. We confirmed in utero fetal Paclitaxel exposure for 8 newborns. Birth details and follow-up to 36 months of age is reported. Meconium samples from newborns exposed to chemotherapy were screened by liquid chromatography-high resolution mass spectrometry while blinded to maternal treatment during pregnancy. Newborn information at birth and annually was obtained. Mean gestational age (GA) at cancer diagnosis and start of chemotherapy was 8.7 + 6.2 weeks and 17.1 ± 3.5 weeks. Paclitaxel was started at a mean GA of 27.0 ± 5.8 weeks. Paclitaxel followed Doxorubicin/Cyclophosphamide in 6 cases, 5-Fluouracil/Doxorubicin/Cyclophosphamide in 1, and was used alone in 1. Mean number of days between Paclitaxel and birth was 23 ± 15. Identification of Paclitaxel and/or metabolites was made in all meconium from paclitaxel-exposed fetuses. Birthweight was < 10% for GA in 3 infants. Three anomalies occurred: mild hip dysplasia without further treatment and mitral valve stenosis. The third child was diagnosed with Cleidocranial Dysostosis, a familial anomaly. Mean age at pediatric follow-up is 18.7 + 9.3 months. Pediatricians report eczema and recurrent otitis media in 1 child, iron deficiency anemia and upper respiratory infection in 2. One child is < 10% for height and weight at 15 months. All are meeting developmental milestones at median age of 18.7 months, range: 6–36 months.

Conclusion: Up to 3 years of age, follow-up of neonates exposed to Paclitaxel in utero is reassuring. Continued observation of neonatal development is essential.

What is Known:

• Chemotherapy during the second and third trimester of pregnancy does not result in an increase in congenital malformations or developmental delay.

• In non-human primate studies by Van Calsteren et al., variable plasma and/or tissue concentrations of taxanes, carboplatin, and trastuzumab were encountered in the fetal compartment.

• Pilot data reported by the current investigators proved that paclitaxel crosses the human placenta.

What is New:

• This current article provides medical and developmental follow up on the newborns from this exposure for 3 years after birth.

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Abbreviations

AC:

Anthracycline

BSA:

Body surface area

GA:

Gestational age

LC-HRMS:

Liquid chromatography-high resolution mass spectrometry

MACDP:

Metropolitan Atlanta Congenital Defects Program

WHO:

World Health Organization

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Funding

Support was provided by Richard V. Lee Award NASOM North American Society of Obstetrics in Medicine, Cooper Foundation (Grant #: 402200), and Cooper Medical School of Rowan University (Grant #: 800002).

Author information

Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Cooper University Hospital, 1 Cooper Plaza, Camden, NJ, 08103, USA

    Elyce H. Cardonick & Serwaa Akoto

  2. Virginia Commonwealth University Health System, 1101 E. Marshall St., Sanger Hall Suite 1-030, Richmond, VA, 23298, USA

    Andie E. O’Laughlin

  3. Temple Health, Philadelphia, PA, USA

    Samantha C. So

  4. Cooper Medical School of Rowan University, 401 Broadway, Camden, NJ, 08103, USA

    Lindsay T. Fleischer

Authors
  1. Elyce H. Cardonick
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  2. Andie E. O’Laughlin
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  3. Samantha C. So
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  4. Lindsay T. Fleischer
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  5. Serwaa Akoto
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Contributions

The corresponding author contributed to the study conception and design. All authors assisted with material preparation and data collection. The corresponding author completed data analysis. Corresponding author wrote the first draft of the manuscript and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Elyce H. Cardonick.

Ethics declarations

Ethics approval

This study was approved by the Cooper Health System Institutional Research Board and was performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. Women diagnosed with cancer during pregnancy were offered enrollment in a multicenter cohort study registered with clinicaltrials.gov NCT02749474 that collects diagnostic and treatment information as well as neonatal well-being for this unique cohort of patients.

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All participants gave their informed consent to participate in this study and have de-identified information used in publication.

Conflict of interest

The authors declare no competing interests.

Additional information

Communicated by Gregorio Paolo Milani

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Cardonick, E.H., O’Laughlin, A.E., So, S.C. et al. Paclitaxel use in pregnancy: neonatal follow-up of infants with positive detection of intact paclitaxel and metabolites in meconium at birth. Eur J Pediatr 181, 1763–1766 (2022). https://doi.org/10.1007/s00431-021-04260-3

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  • DOI: https://doi.org/10.1007/s00431-021-04260-3

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